The long term goal of this project is to elucidate the mechanism of sympathetically maintained pain (SMP). Three hypotheses are proposed regarding development of maintenance of SMP after spinal nerve ligation; 1) sympathetic sprouting in the dorsal root ganglion (DRG) is an important causal factor of SMP, 2) this sympathetic sprouting is induced by increased levels of nerve growth factor (NGF) in the DRG, and 3) susceptibility to SMP depends on amount of NGF production in the DRG. Six specific aims are formulated to test these hypotheses in the Chung model of neuropathic rat. Sympathetic sprouting in the DRG (Specific Aim 1) will be assayed by double immunofluorescent labeling of sympathetic fibers for tyrosine hydroxylase (TH) and growth associated protein GAP-43. Sympathetic synaptic endings and contacts and possible sites of sympathetic effects on sensory neurons int he DRG of injured nerve (Specific Aim 2) will be quantified by electron microscopic immunostaining and correlated to neuropathic pain behaviors. The NGF levels in the DRG of neuropathic rats (Specific Aim 3) will be tested by an enzyme linked immunosolvent assay (ELISA) method. The effects of nti-NGF on SMP (Specific Aim 4) will be tested by infusing anti-NGF into the DRG of neuropathic rats and then examining pain behaviors and sympathetic sprouting. The changes of NGF levels and sympathetic sprouting in the DRG of Brown Norwary (BN) and Sasco Sprague-Dawley (SD) neuropathic rats, which are less susceptible to SMP, will be determined (Specific Aim 5) and correlated to pain behaviors. The effects of NGF on SMP in BN and Sasco SD neuropathic rats (Specific Aim 6) will be tested by infusing NGF into DRG of neuropathic rats and examining pain behaviors and sympathetic sprouting. Successful completing of th project should advance our understanding of the mechanisms of SMP and suggest treatments of neuropathic pain patients.